Sunday, December 6, 2009

Subject: Invitation to Author a Review Article

Here is an email sent to one of my psychiatrist colleagues by BlueSpark, a medical communications company working under contract for the drug company sanofi-aventis. Read it, and decide whether you think this is a solicitation to become a ghost author.

Subject: Invitation to Author a Review ArticleDate: Dec 2009

Dear Dr. XXXXXXX,

I hope this note finds you well. My name is Jonathan Wert, MD, and I am a medical director at BlueSpark Healthcare Communications, a medical communications company located in northern New Jersey. I was given your contact information by Dr. YYYYYYY , who spoke very highly of you.

I am writing to you on behalf of sanofi-aventis, which has authorized us to facilitate publication of an MDD/Bupropion-focused review article. We feel that your input on a multitude of topics including the following would be extremely valuable:

* Your views on MDD, including the variability in response to treatment.* How MDD is currently being treated and how successful these treatments are at inducing remission and preventing relapse.* What are the other benefits of available therapies?* What are the unmet needs/drawbacks of these medications?* What attributes novel antidepressants should have.

sanofi-aventis and BlueSpark would be pleased to have you serve as the author of this article, and we will work closely with you in its development. Initially we will help develop a draft outline. Once you have reviewed and approved this outline, we will proceed to development of a draft paper. We will then revise the manuscript according to your direction and assure that it is styled appropriately for submission to your proposed journal.

As I am sure you are very busy, our team would like to arrange a brief conference call to discuss the content to be included in the manuscript/outline. I look forward to hearing from you at your earliest convenience.

Best regards,Jon

Jonathan M. Wert, MD, MAAP

Here’s the way I interpreted the letter.

Sanofi-aventis just introduced a “new” antidepressant called Aplenzin. Aplenzin is not really new at all, being simply a reformulated version of bupropion extended release. Its advantage is that it offers once a day dosing in all three of the usual doses prescribed (150 mg, 300 mg, and 450 mg), whereas generic bupropion ER offers once daily dosing for 150 mg and 300 mg only. The unusual patient who needs 450 mg dose has to combine 150 mg with 300 mg. So from a clinical standpoint, Aplenzin represents an “advance” in the most minutely incremental sense.

The disadvantage of Aplenzin is not so subtle. It is a health care budget-buster, costing 20 times more than generic bupropion ER. Where do I get this figure? Vermont’s Pharmaceutical Marketer Price Disclosure Law requires that drug companies disclose their drug’s wholesale price along with the prices of drugs in the same class. It turns out that the starting dose of Aplenzin costs $5.58, while the same dose of generic Bupropion ER costs only 28 cents. I’m sure Obama would be pleased to hear about this!

Obviously, selling Aplenzin is going to be an uphill battle, so along with the usual journal ads and drug rep visits, sanofi-aventis has added a publication plan to their marketing strategy. Here’s where Dr. Wert and BlueSpark come in. BlueSpark is looking for doctors to write, as they put it, an “MDD/Bupropion-focused review article.”

Although the letter is artfully crafted to make it appear that they are simply seeking the good doctor’s “input” on some issues, the flavor of input they are after is clear if you read between their lines. I’ve taken the liberty of deciphering the coded language used by BlueSpark, in order to further clarify the nature of their solicitation.

*“Your views on MDD, including the variability in response to treatment.”[You should say that lots of patients don’t respond to SSRIs or to the usual doses of bupropion, in order to set up the conclusion that Aplenzin is useful.]

* “How MDD is currently being treated and how successful these treatments are at inducing remission and preventing relapse.”[Here, your focus will be on how SSRIs are often not successful at achieving remission, so you better try Aplenzin.]

* “What are the other benefits of available therapies?”[Similar to the point above, namely, say that available therapies suck, so hurray for Aplenzin].

* “What are the unmet needs/drawbacks of these medications?”[The main drawback: nobody is prescribing Aplenzin yet]

* “What attributes novel antidepressants should have.”[Best attribute: be a once a day version of bupropion like Aplenzin].

I got a response from Michael Weems, BlueSpark’s COO, who disagreed with my assessment, saying that I had “misunderstood” his invitation: To quote from his response: “Any development of a draft manuscript would take place only after the author has developed a formal outline that would include tables, figures, and references. Following this, the author would review the draft manuscript and have total control of the content (ie., change, add, remove, or edit as he or she sees fit to meet the manuscript objectives). Our role would be to facilitate the development of the article by helping the author publish the article in a timely fashion. Additionally, our support is always acknowledged and can also lead to co-authorship if it meets the guidelines defined by the ICJME.”

As I read Mr. Weems’ letter, my built-in BS detector went as wild as a Geiger counter in Iran. Because let’s face it. No psychiatrist is going to wake up in the morning and say, “I think today is the day I’ll work on a review article on bupropion and depression and how awful it is that the tiny number of patients who require the maximum dose have to take two pills in the morning instead of one. Yes—this will be a significant contribution to the medical literature.”

This would never happen, because there’s nothing new or interesting in this topic. We know that bupropion works well for depression, and we’ve known it even since it was approved by the FDA in 1985.

No, the only reason a psychiatrist would get motivated to write such an article is if a cold-call email solicitation from BlueSpark gets past the spam filter. I’m guessing that BlueSpark hopes that eventually they will find an uncreative,mid-level academic who is treading water professionally, and who will jump at the chance to pocket a little extra money while simultaneously padding the resume with a publication that will require essentially no work to produce. (Dr. Wert’s line at the end of his solicitation, “As I am sure you are very busy…” seems a nudge-nudge wink-wink assurance that the company will take care of everything.)

Whether or not this meets the formal definition of ghost-writing, it is clearly a manipulation of the medical literature, a kind of plastic surgery of science. The articles may look impressive, and they may look real, but in fact they will be phony.

The most telling part of BlueSpark’s response to me came at the end of the COO's letter:

“Based on your misunderstanding of our invitation, we are requesting that you do not post this letter on your blog. If you have any additional questions or would like to discuss this topic further, please e-mail me or call me directly at the number below.”

Does this mean that if I had understood the invitation, they would have been happy to see it posted? I doubt that. Or was this simply BlueSpark’s effort to bully me into keeping this embarrassing letter out of the public eye?

If so, I guess it didn't work.

Abe Lincoln put it well: “You can fool some of the people all of the time, and all of the people some of the time, but you cannot fool all of the people all the time.” For all of our sake, let’s hope this holds as true in the 21st century as it did in the 19th.

30 comments:

Actually, “Read it, and decide whether you think this is a solicitation to become a GUEST author” is meant.

Background into authorship ethics is needed.

First, a primer with definitions:From the American Medical Writers Association, “AMWA Ethics FAQs” (www.amwa.org/default.asp?id=466), which I wrote: Q: What do “ghost authoring,” “guest authoring,” and “ghostwriting” mean?A: “Ghost authoring” refers to making substantial contributions without being identified as an author. “Guest authoring” refers to being named as an author without having made substantial contributions. “Ghostwriting” refers to assisting in presenting the author's work without being acknowledged. The term “ghostwriting” is often used to encompass all three of these practices.

For additional background, I strongly suggest reading the following:Chris Graf and others for the International Society for Medical Publication Professionals [ISMPP; www.ismpp.com]. Good Publication Practice for Communicating Company Sponsored Medical Research: The GPP2 Guidelines. Available for free at *www.bmj.com/cgi/content/full/339/nov27_1/b4330*.

In an entry, “How Industry Views the Research It Sponsors” (Monday, November 30, 2009) at the Health Care Renewal blog (http://hcrenewal.blogspot.com), Roy M. Poses, MD, trenchantly criticized GPP2. He wrote in part, “The guidelines thus appear to condone ghost-[authoring] in its most pernicious form.” The comments section of this blog post includes my comment (December 3, 2009,12:48:00 PM EST), elaborating on Dr. Poses' statement that I quoted here.

To help make a better decision about the situation described on this blog entry, see The BMJ (“helping doctors make better decisions") Submitting an article to the BMJ (http://resources.bmj.com/bmj/authors/article-submission)

Who prompted this submission?We may ask authors submitting or offering unsolicited articles, particularly reviews and editorials covering topics with related commercial interests, several questions before proceeding. Even if the answers to all of these questions were "yes", we wouldn't necessarily reject the proposal or article. We appreciate that companies can commission some excellent evidence based work and that professional writers can present that evidence in a particularly readable and clear way that benefits readers and learners. We would, however, expect such companies' and writers' contributions to be mentioned in the article. And we would want to know that the BMJ article did not overlap by more than 15% with any similar publications or submissions written by the same authors elsewhere. Here are the questions:• has anyone (particularly a company or public relations agency) prompted or paid you to write this article?• would/did a professional writer contribute to the article, and to what extent? • would the BMJ article be original, or would it be similar to articles submitted or published elsewhere?

Michael, I'm not certain what your point is. Clearly, journals want to publish articles of genuine scientific merit rather than veiled promotional puff pieces. BlueSpark is clearly using sanofi aventis' money to recruit a doctor to write an article that will be a promotional piece for its sponsor's product. You can slice up the vocabulary however you want (ghostwriting, guest writing, ghost authoring, whatever), but the what is being done here is a corruption of the academic process in name of promotion.

Danny, my point is to help readers by providing background to help them understand the issues. Part of the problem in discussing ghostwriting is that the words are not understood.

I should have noted that AMWA Ethics FAQs not only provides definitions, but also explains why issues such as the ones that you discuss in your blog entry are so important. With such a background, one can better evaluate what you blogged about.

I have not shaped my opinion about your blog entry and so I limited my comments to background. As first impressions, I am disturbed about what you wrote, and I understand that application of GPP2 would discourage the sort that you invitation letter that you describe.

After reading this post and some of the comments, just another example of how people rationalize and minimize the slippery path to compromise and greed/prestige. When are doctors, psychiatrists in this case, going to finally accept that their collusion with the pharmaceutical industry has done more damage than good for patient care? I wrote a letter to Ronald Pies following his recent editorial piece in the Nov issue of Psychiatric Times basically the same question, a bit more verbose though, and I know I will not get an answer. Everyone seems to be in the back pocket who has money or leverage to gain in this field. And shame on all of you who look the other way if you are not complicit or just uninterested in these shenanigans.

Interesting to see a Sunday posting, Dr Carlat. Hope you are feeling better and getting back into the groove.

PS: Health care reform will be the final nail in the coffin of burying psychiatry, mark my words. After all, our PCP/Family Doctor/NP/OBGYNs are showing they can write RXs just as well as us, and will cost less to reimburse the effort. Hmm, how fascinating for all the past 15 or so years after relinquishing the role as therapists and just being hydraulic lift operators, someone cheaper can fit the bill. How ironic the end to that last sentence, eh? All you doctors being silent as this death sentence is being crafted in DC, enjoy your last few years. Here's my new punch line: take two generic ASAs and call your congressman in the morning, 'cause that's who's gonna decide your treatment strategies by 2014.

I see a psychiatrist once a month who has prescribed me a perhaps unusual--but generally effective--combination of two 150mg Bupropion SRs and 45mg fast-dissolve Miritzipine for depressive and OCD symptoms. In Ontario Canada the Ministry of Health provides drug coverage for Bupropion SR but, for some reason, does not cover the XR.

I would disgree slightly about minimising the "inconvenience" of taking 2 Wellbutrins if this means that one has to be taken in the morning and one in the afternoon. I can attest to the fact that this takes practice--you always need to make sure you have water on you, you can't lose track of time and you can't forget to keep a vial of "extras" for consumption outside of the home. It's much simpler to just take one pill in the morning, and if this is what Aplenzin does I would say, from a consumer's POV, that it's worth a look.

The letter to Danny Carlat from the medical director at BlueSpark is indicative of an aspect of human nature that probably hasn’t changed much in the past 100 years.

It is called rationalization.

The nature of the original request is pretty obvious – the medical communications company is offering to develop the outline and draft. All they want from the doctor is for him to rubberstamp the article once completed.

If anyone has doubts about that, please reread the following paragraph. It clearly states that sanofi-aventis and Blue Spark will help develop the outline and draft.

“sanofi-aventis and BlueSpark would be pleased to have you serve as the author of this article, and we will work closely with you in its development. Initially we will help develop a draft outline. Once you have reviewed and approved this outline, we will proceed to development of a draft paper.”

Folks, this is not rare. It is standard fare, and is just as common as it always has been. Academics have hard time-saying "no" to an easy publication (academic currency) and easy money (real world currency). The pharmaceutical and medical device companies know this. All the "supplemental" issues to major medical journals, "proceedings from symposium" and second and third tier journals are filled with this garbage. It is a perversion of the medical literature, no matter what name we give it.

In fact, Aplenzin does not even offer the small benefit of allowing once a day dosing, because existing generic formulations of extended release bupropion can also be taken once a day--which I agree is a real benefit over twice a day dosing. No, Aplenzin's only benefit is that at the highest recommended dose of bupropion (450 mg/day), it can be taken as a single pill in the morning, whereas generic bupropion ER would have to be taken as two pills in the morning: one 300 mg pill and one 150 mg pill. For patients who hate swallowing pills at all, and who therefore might underdose themselves in order to avoid having to take two pills, Aplenzin would offer a convenience advantage. And remember this would only apply to patients taking 450 mg, which is an uncommonly prescribed dose.

Bottom line, yes, there is one coneivable clinical situation for which Aplenzin might represent an "advance," but such a situation is rare and does not outweigh the hugely inflated price of the sanofi aventis me-too product.

The doctor who forwarded me this email did not respond to the request and is disgusted by the idea of drug companies having doctors do these kinds of underhanded promotional activities. I have no idea how much he would have been paid, if anything. There was no mention of payment in the letter. Other colleagues have told me that such payments are not huge as a rule--maybe in the range of $1000-$2000. The real "payment" is the fact that the medical writing company does the enormous amount of grunt work involved in substantially writing and researching the article and getting it published in a journal. And the identified author gets to add the publication to the CV, which helps his or her career.

A Carlat Psychiatry Blog entry, “Medscape’s CME Corruption” (Friday, June 13, 2008), described a cased-based CME program, “Managing Schizophrenia in a Patient With Alcohol Abuse and Hepatic Impairment” sponsored by Janssen, “focussing on the single clinical situation in which [Janssen’s] Invega has an advantage.” As the blog entry noted, “Invega is simply a patent extender, with no real benefit other than the fact that it is not metabolized in the liver, and therefore is easier to dose in patients with hepatic impairment.” Accordingly, the CME program focused on a schizophrenia patient with liver impairment for whom Invega was the appropriate choice.

A case-based CME program focusing on the uncommon clinical situation in which Aplenzin has an advantage could be developed, if it isn’t being done already.

A Carlat Psychiatry Blog entry on Friday, June 13, 2008, “Medscape's CME Corruption”, discussed bias in a CME program, "Managing Schizophrenia in a Patient With Alcohol Abuse and Hepatic Impairment". This program was sponsored by Janssen, maker of Invega (paliperidone). According to the blog entry, Invega has no real benefit except that it is not metabolized in the liver, making it easier to use in patients with liver impairment.

Janssen commissioned Medscape to come up with a case-based program focussing on the single clinical situation in which Invega has an advantage, the blog entry explained. The CME program’s case study asked about a medication change for a alcohol-abusing, liver-impaired schizophrenia patient. The correct choice was Invega.

Given Dr. Carlat’s assertion that sanofi-aventis’s new antidepressant, Aplenzin, offers an advantage only in an uncommon situation, that of one-tablet daily dosing in patients who take the highest dose, 450 mg, could a case-based CME program be developed to focus on the single clinical situation in which Aplenzin has an advantage? Or maybe such a CME program is already in development.

According to Dr. Carlat, bupropion works well for depression, so the issue here is not one of a lousy drug.

I found on Drugs@FDA (http://tinyurl.com/3hhaw), a helpful website, that sanofi-aventis’s antidepressant, Wellbutrin (bupropion hydrochloride) was FDA-approved 1985. It has to be taken three times a day. In 1996, the FDA approved a twice-daily formulation, Wellbutrin SR. Then in 2003, the FDA approved a Wellbutrin formulation, Wellbutrin XL, for once-daily dosing. At the lower two of the three doses, only one tablet needs to be taken, but at the highest dose, two tablets have to be taken. This once-daily formulation is available as a generic in the United States.

In 2008, the FDA approved sanofi-aventis’s Aplenzin (bupropion hydrobromide). Only one tablet needs to be taken daily, even at the highest dose.

sanofi-aventis uses this advantage for marketing to consumers. From www.aplenzin.com: “Simply one of the things you’ll do today. Aplenzin is the once-daily tablet with the benefits of bupropion. Simply convenient. One pill, once-daily may be all you need. Aplenzin allows you to not worry about the number of tablets so that you have a simpler, more convenient dosing regimen for the treatment of major depressive disorder. Talk to your doctor to see if Aplenzin is right for you.”

I do not know how sanofi-aventis markets Aplenzin to prescribers.

Your doctor might wonder if an article in the scientific literature makes Aplenzin right for you. Certainly it is more convenient to have to take only one pill once a day. But you can already do that at the two lower doses with generic form of Wellbutrin XL, as Dr. Carlat explains, and, as Dr. Carlat continued, only a few patients need the highest dose at only one tablet daily.

From a marketing perspective, wouldn’t it be handy for your doctor to have a bupropion-focused review article “authored” by an expert working with a MECC paid by sanofi-aventis?

Simply obvious.

Or might I be simply jaded? Talk to your ethicist to see if working on such an assignment as a medical writer is right for you.

The reply from BlueSpark to Dr. Carlat seems to have backed off from BlueSpark’s invitation to Dr. XXXXXXX. The invitation states that BlueSpark was to arrange a “brief conference call to discuss the content to be included in the manuscript/outline” with Dr. XXXXXXX, prepare the outline, have Dr. XXXXXXX approve the outline, and then BlueSpark would write the article. But BlueSpark’s letter to Dr. Carlat states that writing would take place only after the author developed a formal outline.

I would like to see an article in which a BlueSpark staff member is named as a coauthor or given an acknowledgment.

I’ve been uneasy about the development of outlines by MECCs with little author input. I sense that it gives the MECC too much leeway to influence content. How does a journal editor invite a review article?

A better way to reach an ethical approach is to ask the prospective author to collect references, highlight the main points, provide his or her own talking points, provide slides from presentations, and then have the writer write. Such an approach to an author-writer relationship could be part of a writer’s standard operating procedure (SOP), as discussed by Karen Woolley in her article, “Goodbye ghostwriters! How to work ethically and efficiently with professional medical writers. Chest 2006;130:921-923 (available at _www.chestjournal.org/content/130/3/921.full.html_): “The SOP should clarify that authors are responsible for identifying the key messages and data to be presented in the manuscript.” A limitation of Dr. Woolley’s article is that it refers only a situation in which an author writer work together relationship without involvement of a pharmaceutical company and a MECC in developing a manuscript.

Dr. Woolley’s article was the “Medical Writing Tip of the Month” in the journal Chest’s Postgraduate Education Corner, useful feature.

Michael--Thanks for you informative comments. There is a clearly a spectrum of ghost publication activities. From my viewpoint, the essence of the deception is when drug companies add "publication planning" to their promotional strategy. Publication planning means imbuing the medical literature with content that promotes your product. Advertising is the primary motivation, while communicating accurate and relevant science is secondary. This kind of manipulation of health information is unethical and must end.

The information that you provided does not indicate if an honorarium was to be paid to the author of the review article. According to ISMPP’s good publication practice guidelines (GPP2), which I cited in my comment of December 6, 2009, 9:58 AM, “We recommend that no honorariums are paid for authorship of peer reviewed articles or presentations.” sanofi-aventis is a gold-level corporate sponsor ($10,000 annually) of ISMPP.

It's not even a requirement. Anything that is even kind of sciency will be so obfuscated that no-one could pin it down. Any benefit the article seems to be alluding to will, if the pharma is called on it, be put down to your misreading.

That's what communications people are trained to do.

I doubt this practice can ever be completely shut down because it relies for its success on physician's egos.

From “Good publication practice for communicating company sponsored medical research: the GPP2 guidelines” for the International Society for Medical Publication Professionals (ISMPP; www.ismpp.org; www.bmj.com/cgi/content/short/339/nov27_1/b4330?rss=1), “We recommend that no honorariums are paid for authorship of peer reviewed articles or presentations.”

sanofi-aventis is a gold-level corporate sponsor of ISMPP, which costs $10,000 annually.

In trying to parse this post and all the comments, I feel like I need some medication.

Whatever else the problems here -- and I don't know enough to contest the issue -- it is NOT unusual for academics to need help in formulating their thoughts and writing a cogent article.

Plenty of academic book authors present the most basic of outlines to their "co-authors" (who are not named), and through conversations the content is fleshed out. Drafts are written and edited in back-forth fashion.

After trying to parse this post and all the comments, I feel like *I* need some medication.

Whatever else the problems here -- and I don't know enough to contest the issue -- it is NOT unusual for academics to need help in formulating their thoughts and writing a cogent article.

Plenty of academic book authors present the most basic of outlines to their "co-authors" (who are not named), and through conversations the content is fleshed out. Drafts are written and edited in back-forth fashion.

Do you have evidence that such articles are influenced by the pharma company that sponsors the facilitating of the writing?

How does it work exactly? Do you contract to write the article with the writer, for example, and are you guaranteed approval of any edits?

If so, why is this a problem? Why was this doctor so offended? Presumably he views his opinions as above reproach and incorruptible, so why would he not share his honest opinions in such an article? Would he prefer that a physician with more corruptible morals do the writing?

Isn't it just POSSIBLE that the editor finds merit in such an article (which I think was a review) and wants a well-written article?

In case you're unaware, it takes an immense amount of work to make readable the average text from a non-writer, especially academics. In my experience, it's the toughest editing I've ever done!

I doubt these journal staffs have the editor hours -- not to mention the subject-specific expertise -- to do such a careful edit.

My point is, such issues are not always black and white.

A professional editor for 30 years, I've received NO pharma funding whatsover.

A better way to reach an ethical approach is to ask the prospective author to collect references, highlight the main points, provide his or her own talking points, provide slides from presentations, and then have the writer write. Such an approach to an author-writer relationship could be part of a writer’s standard operating procedure (SOP), as discussed by Karen Woolley in her article, “Goodbye ghostwriters! How to work ethically and efficiently with professional medical writers. Chest 2006;130:921-923 (available at _www.chestjournal.org/content/130/3/921.full.html_):

I bring to your attention a concern about the lack of effectiveness of generic bupropion.

An acquaintance of mine is patient who has done well on Wellbutrin (branded buproprion) but not on the generic. (S)he adds that (s)he is aware of a number of other patients who also did well on Wellbutrin, switched to generic and deteriorate, and then switched back to Wellbutrin and did well.

The concern is from the concern about the usefulness of Aplenzin that Dr. Carlat raised and from the concern about authorship ethics that I raised.

Thanks so much for sharing an "invitation" that few of us would get a chance to read.

I'm not a physician - just a heart attack survivor who now takes a fistfull of cardiac meds every day, and who has become increasingly alarmed since realizing that I have no clue which of my meds were prescribed to me based on these tainted journal articles or flawed research bought and paid for by Big Pharma - AND NEITHER DO MY DOCTORS.

Dr. Carlat, you have hit the nail on the head with your comments about how much academics are paid by drugmakers to lend their names to ghostwritten pieces.

The real value is worth far more than cash. In academia, where 'publish or perish' is the law, a nice fat list of journal publications on your CV affects tenure, promotion and grant applications. And really, who has the time to write your own scientific papers to submit to medical journals?

Secondly, to Gina Pera: you are missing the point here when you write, correctly: "It is NOT unusual for academics to need help in formulating their thoughts and writing a cogent article". Maybe so, but this is not EDITING assistance we're talking about here. Physicians read and trust medical journals, and several studies have shown that prescribing habits are influenced and changed by what docs read.

Journalist Stuart Laidlaw of the Toronto Star explained this in his medical ethics column of August 31,2009 called, ”Ghostwriting: What’s The Harm?”:

“No reporter would discount the role of a good editor. Any story that appears in a newspaper has been edited two or three or more times before it appears in print. This is not ghostwriting. Ghostwriting happens when an anonymous writer prepares an article that is edited by a respected researcher in the field. The editor’s name then appears on the paper as author. No newspaper I know assigns bylines that way.”

More at: "Partners in Slime: Why You Should Be Alarmed by Medical Ghostwriting" http://www.ethicalnag.org/2009/09/05/partners-in-slime/